Background: Mortality following acute myocardial infarction (AMI) has decreased in western countries for decades; however, it remains unknown whether the decrease is distributed equally across the population independently of residential location. This study investigated whether the observed decreasing 28-day mortality following an incident AMI in Denmark from 1987 to 2016 varied geographically at municipality level after accounting for sociodemographic characteristics. Methods: A register-based cohort study design was used to investigate 28-day mortality among individuals with an incident AMI. Global spatial autocorrelation (within sub-periods) was analysed at municipality level using Moran's I. Analysis of spatio-temporal autocorrelation before and after adjusting for sociodemographic characteristics was performed using logistic regression and conditional autoregressive models with inference in a Bayesian setting. Results: In total, 368,839 individuals with incident AMI were registered between 1987 and 2016 in Denmark; 128,957 incident AMIs were fatal. The 28-day mortality decreased over time at national level with an odds ratio of 0.788 (95% credible interval (0.784, 0.792)) per 5-year period after adjusting for sociodemographic characteristics. The decrease in the 28-day mortality was geographically unequally distributed across the country and in a geographical region in northern Jutland, the 28-day mortality decreased significantly slower (4–12%) than at national level. Conclusions: During the period from 1987 to 2016, the 28-day mortality following an incident AMI decreased substantially in Denmark. However, in a local geographical region, the 28-day mortality decreased significantly slower than in the rest of the country both before and after adjusting for sociodemographic differences. Efforts should be made to keep geographical trend inequalities in the 28-day mortality to a minimum.